Substance use has acute and chronic detrimental impacts on public health. However, risk for use is not conferred equally across the population, the life course, or birth cohorts. Central questions about when and for whom risk factors are most important in contributing to substance use (tobacco, alcohol, marijuana, and other drug use) in young adulthood (YA) remain unanswered, including the extent to which substance use in YA leads to adult health consequences such as substance use disorders (SUDs), sexual risk behaviors, and physical/mental health deficits. Based on a life course perspective, this project will move the field toward examining developmental changes in the salience of risk factors across the life course and toward documenting the mechanisms through which long-term substance use consequences emerge. We will use national panel data from 38 high school senior year cohorts (1976 to 2013), with specific emphasis on 20 cohorts of individuals with longitudinal data across ages 18 to 35 (N~24,000) from Monitoring the Future (MTF) to examine significant unanswered questions regarding adolescent and YA substance use behaviors and adult health outcomes. Leading-edge statistical methods applied to MTF data will be used to model the dynamic associations between risk factors and risk behaviors across YA, and the extent to which these behaviors predict adult health consequences. Aim 1 will examine questions regarding developmental changes in the epidemiology and etiology of substance use across ages, cohorts, social role statuses, and demographic subgroups. Questions include the extent to which the links between cognitive/attitudinal risk factors and substance use behaviors change with age. Aim 2 will examine the long-term consequences of YA substance use on the acquisition and timing of social role statuses and health into adulthood. For example, we will examine the extent to which social roles mediate the effect of YA substance use on adult health consequences. Aim 3 will focus on disseminating new and advanced methodological techniques for examining risk factors, behaviors, and consequences to public health researchers. Results will advance our understanding of substance use behaviors with critical health impacts, and will inform the development of interventions that take into account individual behaviors, risk factors, and social roles to find strategies for reducing the negative consequences of drug use in young adulthood.